With modern intensive combination
polychemotherapy, the complete response (CR) rate in adults with
acute lymphoblastic leukemia (ALL) is 80% to 90%, and the cure rate is 40% to 50%. Hence, there is a need to develop effective
salvage therapies and combine novel agents with standard effective
chemotherapy. ALL leukemic cells express several
surface antigens amenable to target
therapies, including CD20, CD22, and CD19.
Monoclonal antibodies target these leukemic
surface antigens selectively and minimize off-target toxicity. When added to frontline
chemotherapy,
rituximab, an antibody directed against CD20, increases cure rates of adults with
Burkitt leukemia from 40% to 80% and those with
pre-B ALL from 35% to 50%.
Inotuzumab ozogamicin, a CD22
monoclonal antibody bound to
calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6 to 7 months when given to patients with refractory-relapsed ALL.
Blinatumomab, a biallelic T cell engaging the CD3-CD19
monoclonal antibody, also resulted in overall response rates of 40% to 50% and a median survival of 6.5 months in a similar refractory-relapsed population. Other promising
monoclonal antibodies targeting CD20 (
ofatumumab and
obinutuzumab) or CD19 or CD20 and bound to different
cytotoxins or
immunotoxins are under development. Combined modalities of
chemotherapy and the novel
monoclonal antibodies are under investigation.